AB0857 ANTI-THYMOCYTE GLOBULIN EXPOSURE IS ASSOCIATED WITH TREATMENT RESPONSE IN PATIENTS WITH DIFFUSE CUTANEOUS SYSTEMIC SCLEROSIS UNDERGOING AUTOLOGOUS HAEMATOPOIETIC STEM CELL TRANSPLANTATION
Authors: Y. H. Chiu, A. Drijver, R. Admiraal, A. Van Rhenen, S. Nierkens, J. M. Van Laar, J. Spierings
Journal: Annals of the Rheumatic Diseases (2023)

<h3>Background</h3> Autologous haematopoietic stem cell transplantation (HSCT) ameliorates event-free survival, skin thickening and lung function in patients with progressive diffuse cutaneous systemic sclerosis (dcSSc). Anti-thymocyte globulin (ATG) is a key lymphoablative constituent of conditioning protocols and is administered in a body weight-based dose. Response to HSCT and occurrence of infections is still highly variable across dcSSc patients. Studies in haemato-oncological patients suggest that ATG exposure varies across subjects and impacts outcomes [1]. <h3>Objectives</h3> To explore the relation between rabbit derived ATG exposure, lymphocyte reconstitution and clinical outcomes in patients with dcSSc undergoing autologous HSCT. <h3>Methods</h3> We retrospectively analysed patients with dcSSc undergoing autologous HSCT between 2014 and 2020. ATG levels were measured in cryopreserved serum samples at four time points (day 1 and week 1, 2 and 4) after stem cell reinfusion. ATG exposure was estimated using population pharmacokinetics models [1]. Treatment response was defined as pulmonary stabilisation (with no decline more than 10% in forced vital capacity and 15% in diffusing capacity for carbon monoxide) and/or skin improvement (modified Rodnan skin score reduction of more than 30%). Differences between groups were examined with Wilcoxon rank-sum test for contentious variables and Fisher exact test for categorical variables. <h3>Results</h3> Fifteen patients were included in this study with median age 43 years-old (IQR 37–50). During a median follow-up of 45 months (IQR 19—66), 73% (n=11) of patients had a treatment response, and 27% (n=4) were non-responders. Eight (73%) responders achieved long-term remission and three (27%) responders had progressive disease in the follow-up, at a median time of eight months (IQR 5—17) post-HSCT. Although all patients received the same weight-based ATG dosage (7.5 mg/kg), ATG exposure varied across patients. ATG exposure was higher in responders than non-responders (p = 0.026, Table 1) but was not correlated with lymphocyte reconstitution or infection rate. <h3>Conclusion</h3> In our study, ATG exposure highly varied across dcSSc patients undergoing HSCT despite the same weight-based dosage. Responders had a higher ATG exposure than non-responders. More research into optimal ATG dosing is needed to improve HSCT outcomes. <h3>References</h3> [1]Admiraal R, Nierkens S, de Witte MA, et al. Association between anti-thymocyte globulin exposure and survival outcomes in adult unrelated haemopoietic cell transplantation: a multicentre, retrospective, pharmacodynamic cohort analysis. Lancet Haematol 2017;4(4):e183-e91. The median (interquartile range) anti-thymocyte globulin (ATG) exposure was presented in the cumulative area under the concentration–time curves (AU*day/mL). <h3>Acknowledgements</h3> The authors want to thank all patients participating in this study and the department of Medical Microbiology UMC Utrecht, for providing the cryopreserved serum samples. <h3>Disclosure of Interests</h3> Yu-Hsiang Chiu: None declared, Anouk Drijver: None declared, Rick Admiraal: None declared, Anna van Rhenen: None declared, Stefan Nierkens: None declared, Jacob M. van Laar Grant/research support from: Grant from Boehringer, Astra Zeneca, MSD, Roche., Julia Spierings Grant/research support from: A grant from Boehringer.